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Abstract

Proton MR spectroscopy (MRS) provides an effective tool for measuring metabolites in human brain noninvasively. Precise measurement of several clinically important metabolites such as glycine (Gly), 2-hyroxyglutarate (2HG), gamma-aminobutyric acid (GABA), and glutamate (Glu) remains challenging primarily due to their relatively small signal strengths and spectral overlap with adjacent large signals. The present study aims to develop new MRS techniques for reliable imaging of these metabolites and apply in brain tumor patients at 3T and 7T. The transverse relaxation times (T₂) of brain metabolites are needed for absolute quantitation. As the ﬁrst topic, the T₂s of metabolites in healthy brain were measured using point-resolved spectroscopy (PRESS) at 3T. The T₂s of Glu, myo-inositol, NAA-aspartate, and N-acetyl-aspartyl-glutamate were evaluated in addition to large singlet signals. The second topic was to measure Gly in human brain with MRS imaging at 3T. An optimized PRESS TE=160 ms scheme was used to measure Gly in healthy brain and brain tumors. The data indicated the presence of a regional variation of Gly in healthy brain, with estimates ∼1 mM and ∼0.3 mM in gray and white matter dominant regions, respectively. The Gly level was significantly increased in tumors compared to the contralateral brain. Gly elevation was more extensive with higher tumor grade. Mutations in isocitrate dehydrogenase (IDH) 1 and 2 result in production of 2HG and as a result, 2HG is elevated by orders of magnitude in IDH-mutated gliomas. As the third topic, 2HG was estimated in subjects with IDH-mutated gliomas using MRS imaging. PRESS TE=97 ms and 78 ms were used for detection of 2HG at 3T and 7T, respectively. The reproducibility of 2HG MRS was evaluated at 3T. The MRS measurement of 2HG was reliable and highly reproducible, suggesting that the methods can be used as a noninvasive diagnostic/prognostic tool in brain tumors. GABA, a primary inhibitory neurotransmitter, is implicated in a variety of neuropsychiatric disorders. As the fourth topic, GABA level in healthy brain was evaluated using PRESS TE=92 ms at 7T, which was optimized for separating the GABA and Glu signals between 2.2 and 2.4 ppm. The data from multiple brain regions indicated that GABA is higher by 7 - 8 fold in gray matter regions than in white matter regions.